56-53-1 Usage
Chemical Properties
Diethylstilbestrol is an odorless, white crystalline powder, with a molecular weight of 268.36. Its cisisomer tends to revert to the trans-form. It is a nonsteroidal, synthetic stilbene derivative with estrogenic activity. recomended solvents are DMSO, DMF and ethanol, even in these solvents do not store in solution for any prolonged period of time.
Originator
DES,Amfre-Grant,US,1946
Uses
Different sources of media describe the Uses of 56-53-1 differently. You can refer to the following data:
1. Diethylstilbestrol has been used:to evaluate the estrogenic activity of diethylstilbestrol by quantitating the expression levels of endogenous estrogen-regulated marker genesto evaluate the estrogenic, androgenic and toxicity responses in bioluminescent yeast bioreporter assay (BLYES)to detect its effect on the proliferation and tyrosinase activity of melanocytes
2. Diethylstilbestrol is a synthetic nonsteroidal estrogen that was
formerly used in estrogenic hormone therapy (for menstrual
disorders, postpartum breast engorgement, postcoital contraceptive,
prevention of spontaneous abortion) and in chemotherapy
of various cancers, including postmenopausal breast
cancer and prostate cancer. It was also used in biomedical
research and veterinary medicine (growth promoter for cattle
and sheep; veterinary drug to treat estrogen deficiency disorders).
Indications
Diethylstilbestrol is one of the older synthetic estrogens in use. It was used to treat prostate cancer but is now rarely used for this purpose because of its adverse effects，although it is occasionally used in postmenopausal women with breast cancer. It is taken orally in tablet form.
Definition
ChEBI: Diethylstilbestrol is an olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups. It has a role as an antineoplastic agent, a carcinogenic agent, a xenoestrogen, an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor, an antifungal agent, an endocrine disruptor, an EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor, an autophagy inducer and a calcium channel blocker. It is a polyphenol and an olefinic compound.
Manufacturing Process
50 parts by weight of p-hydroxypropiophenone are dissolved in 200 parts by weight of a 12.5% solution of caustic soda and shaken with 350 parts by
weight of 3% sodium amalgam. The sodium salt of the pinacol thereby
precipitating is reacted with glacial acetic acid, whereby the free pinacol is
obtained (MP 205°C to 210°C, after purification 215°C to 217°C). The yield
amounts to 95% of the theoretical. The pinacol is suspended in ether and
gaseous hydrogen chloride introduced, whereby water separates and the
pinacolin formed is dissolved in the ether, from which it is obtained by
evaporation as a viscous oil (diacetateof MP 91°C). The yield is quantitative.40 parts by weight of pinacolin are dissolved in ethyl alcohol and gradually
treated with 80 parts by weight of sodium under reflux. The solution is
decomposed with water and the pinacolin alcohol formed extracted from the
neutralized solution with ether. The pinacolin alcohol is a viscous oil which is
characterized by a dibenzoate of MP 172°C. The yield is 95% of the
theoretical.A solution of 30 parts by weight of pinacolin alcohol in ether is saturated with
hydrogen chloride at room temperature and the ether solution then agitated
with bicarbonate. After concentration by evaporation it leaves behind the
crude diethylstilbestrol [α,β-(p,p'-dihydroxydiphenyl)-α,β-diethylethylene]
which, when recrystallized from benzene, melts at 170°C to 171°C. The yield
amounts to 75% of the calculated. The total yield of diethylstilbestrol,
calculated on p-hydroxypropiophenone, is 68% of the theoretical.
Brand name
Stilbestrol (Tablicaps); Stilbetin (Bristol-Myers Squibb);Distilbene;Oestro-gynedron;Stilphostrol.
Therapeutic Function
Estrogen
World Health Organization (WHO)
Diethylstilbestrol, a synthetic estrogen which is a stilbene
derivative, was introduced into obstetric practice in the late 1940s and
subsequently widely used for the treatment of threatened abortion. This use was
later shown to be associated with an increased risk of vaginal cancer in the
offspring which resulted in restrictive regulatory action in several countries.
Diethylstilbestrol and other stilbenes remain available in many countries, however,
for the treatment of certain hormone-dependent neoplasms including carcinoma of
the prostate and postmenopausal breast cancer.
(Reference: (WHODI) WHO Drug Information, 77.1, 16, 1977)
General Description
Diethylstilbestrol is an odorless tasteless white crystalline powder. (NTP, 1992)
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Diethylstilbestrol is incompatible with strong oxidizing agents, strong bases, acid chlorides and acid anhydrides .
Fire Hazard
Flash point data for Diethylstilbestrol are not available; however, Diethylstilbestrol is probably combustible.
Biochem/physiol Actions
Diethylstilbestrol is a synthetic estrogen with carcinogenic properties. Causes renal clear-cell carcinoma in Syrian hamster. In humans it causes increased risk of breast cancer, clear cell adenocarcinoma (CCA) of the vagina and cervix, and reproductive anomalies. Used in the treatment of prostate cancer to block the production of testosterone.
Side effects
These include sodium retention and oedema，nausea，gynaecomastia and impotence in men, and venous and arterial thrombosis. It can cause bone pain and hypercalcaemia when used for breast cancer.
Safety Profile
Confirmed carcinogen
producing skin, liver, and lung tumors in
exposed humans as well as uterine and other
reproductive system tumors in the female
offspring of exposed women. Experimental
carcinogenic, neoplas tigenic, tumorigenic,
and teratogenic data. A transplacental
carcinogen. A human teratogen by many
routes. Poison by intraperitoneal and
subcutaneous routes. It causes glandular
system effects by sktn contact. Human
reproductive effects by ingestion: abnormalspermatogenesis; changes in testes, epididymis, and sperm duct; menstrual cycle
changes or disorders; changes in female
ferulity; unspecified maternal effects;
developmental abnormalities of the fetal
urogenital system; germ cell effects in
offspring; and delayed effects in newborn.
Implicated in male impotence and
enlargement of male breasts. Other
experimental reproductive effects.
Mutation data reported. When heated to
decomposition it emits acrid smoke and
fumes. See also ETHINYL ESTRADIOL.
Carcinogenicity
Diethylstilbestrol is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.
Environmental Fate
Diethylstilbestrol is a known teratogen and carcinogen.
Experimental studies using transgenic estrogen receptor
knockout animals suggest that binding and activation of the
estrogen receptor is required to elicit diethylstilbestrol
toxicity. Hence, diethylstilbestrol lesions primarily appear in
tissues enriched with estrogen receptors. Diethylstilbestrol
binds to the estrogen receptor with a very high affinity and
forms a complex with the target tissue. The complex then
internalizes in to the cell and translocates to the nucleus. Once
in the nucleus, diethylstilbestrol may directly bind with the
cellular DNA and cause mutations and unscheduled DNA
synthesis. Diethylstilbestrol is also known to induce
aneuploidy.
Toxicity evaluation
Diethylstilbestrol’s production and use in biochemical
research, medicine, and veterinary medicine may result in its
release to the environment through various waste streams. It
may also be released to the environment during transport,
storage, or disposal. If released to soil, diethylstilbestrol is
predicted to strongly adsorb to the soil. Volatilization from
the dry or wet soil surface would probably be unlikely. The
extent of biodegradation in soil is not known, although
diethylstilbestrol has been shown to be resistant to degradation
in activated sludge. If released to water, diethylstilbestrol
may bioconcentrate in aquatic organisms and strongly adsorb
to suspended solids and sediments. Diethylstilbestrol is expected
to be essentially nonvolatile on water surfaces.
Diethylstilbestrol would not be susceptible to hydrolysis. The
extent of biodegradation in natural waters is not certain,
although diethylstilbestrol has been shown to be resistant to
degradation in activated sludge. If released to the atmosphere,
diethylstilbestrol vapors should rapidly oxidize, primarily by
reaction with ozone. It is expected to exist solely in the
particulate phase in an ambient atmosphere. Particulatephase
diethylstilbestrol may be removed from the air by wet
and dry deposition.
Clinical claims and research
At first glance, it might be surprising that synthetic nonsteroidal molecules such as diethylstilbestrol (DES) could have the same activity as estradiol or other estrogens. DES can be viewed, however, as a form of estradiol with rings B and C open and a six-carbon ring D. The activity of DES analogs was explained in 1946. It was proposed that the distance between the two DES phenol OH groups was the same as the 3-OH to 17-OH distance of estradiol; therefore, they could both fit the same receptor. Medicinal chemists have shown the OH-to-OH distance to be actually 12.1 ? in DES and 10.9 ? in estradiol. In aqueous solution, however, estradiol has two water molecules that are hydrogen bonded to the 17-OH. If one of the two water molecules is included in the distance measurement, there is a perfect fit with the two OH groups of DES. This suggests that water may have an important role for estradiol in its receptor site.It is now generally accepted that the estrogens must have a phenolic moiety for binding, but some investigators propose that the receptor may be flexible enough to accommodate varying distances between the two key hydroxyls. This point about estrogens needing a phenolic ring for high-affinity binding to the ER is critical. Steroids with a phenolic A ring and related phenolic compounds lack high-affinity binding to the other steroid hormone receptors.
Check Digit Verification of cas no
The CAS Registry Mumber 56-53-1 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 6 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 56-53:
(4*5)+(3*6)+(2*5)+(1*3)=51
51 % 10 = 1
So 56-53-1 is a valid CAS Registry Number.
InChI:InChI=1/C18H20O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,19-20H,3-4H2,1-2H3/b18-17-
56-53-1Relevant articles and documents
Diethylstilbestrol-scaffold-based pregnane X receptor modulators
Hodnik, ?iga,Toma?i?, Tihomir,Smodi?, Domen,D'Amore, Claudio,Ma?i?, Lucija Peterlin,Fiorucci, Stefano,Kikelj, Danijel
, p. 551 - 562 (2015/10/12)
Due to its function as a regulator of drug-metabolizing enzymes and transporters, pregnane X receptor (PXR) represents an important factor involved in drug metabolism. In this work, we describe the discovery of diethylstilbestrol-based PXR modulators, which were designed from marine sulfated steroids with PXR agonistic activity, solomonsterols A and B, and our recently reported bazedoxifene scaffold-derived PXR antagonists. The methylated diethylstilbestrol derivative 1 displayed potent PXR agonistic activity with an EC50 value of 10.5 μM, whereas compounds 3, 4 and 6 (IC50 for 6 = 27.4 μM) and diethylstilbestrol (2) itself (IC50 = 14.6 μM) exhibited PXR antagonistic effects in HepG2 cells. The PXR modulatory effects of the synthesized diethylstilbestrol derivatives were further confirmed by the induction of PXR-regulated CYP3A4 expression with compound 1, as well as by the inhibition of the rifaximin-promoted up-regulation of CYP3A4 expression with 2 and its derivative 6.
Anti-proliferative activities of flavone-estradiol Stille-coupling adducts and of indanone-based compounds obtained by SnCl4/Zn-catalysed McMurry cross-coupling reactions
Pathe, Gulab Khushalrao,Konduru, Naveen K.,Parveen, Iram,Ahmed, Naseem
, p. 83512 - 83521 (2015/10/19)
We described the synthesis of flavone-estradiol adducts and indanophen based tamoxifen analogs using a novel SnCl4-Zn reagent via a McMurry cross-coupling reaction and their anti-proliferative evaluation against human cervical cancer cell lines (HeLa) and human breast cancer cell lines (MCF-7 and MDA-MB-231). A library of 32 tamoxifen analogs was synthesized using indanone and propiophenone derivatives and evaluated for anti-proliferative activities. Among them, compounds 3ac, 3ad, 3ae and 3ao exhibited better anti-proliferative potencies (IC50 2.13-3.81 μM) than the drug doxorubicin (IC50 50 2.85 ± 0.17 μM and 2.42 ± 0.23 μM; 3.64 ± 0.28 μM and 2.93 ± 0.14 μM) against breast cancer cells (MCF-7 and MDA-MB-231) respectively and IC50 2.17 ± 0.18 μM and 2.56 ± 0.32 μM against cervical cancer cells (HeLa) respectively than the standard drug. However, compounds 6ac, 6ae, 6af and 6ag showed moderate activity (IC50 10 μM). The structure-activity relationship analysis revealed that the optimal combination of side chains at the para-position of propiophenone and fluoro substituent on the indanone moiety enhanced the anti-proliferative activities of tamoxifen analogs.
THERAPEUTIC FOR HEPATIC CANCER
-
, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
-
, (2010/05/13)
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
Synthesis and biological evaluation of stilbene-based pure estrogen antagonists
Walter, Georg,Liebl, Renate,Von Angerer, Erwin
, p. 4659 - 4663 (2007/10/03)
The nonsteroidal estrogen diethylstilbestrol can be converted into potent antiestrogens devoid of agonist activity by introduction of side chains with appropriate functional groups. Replacement of one of the ethyl substituents in diethylstilbestrol by side chains with functional groups converted this potent estrogen into pure antiestrogens with the potential for the treatment of breast cancer. These agents completely suppressed estrogen receptor-mediated gene activation and inhibited the growth of estrogen-sensitive MCF-7 breast cancer cells in submicromolar concentrations. The most potent derivative displayed similar activity as fulvestrant (ICI 182,780) in vitro and in the mouse uterine weight test. Obviously, the stilbene structure can act as a substitute for estradiol in the development of pure estrogen antagonists.
Selectivity control by chemical modification of the recognition sites in two-point binding molecularly imprinted polymer
Lee, Kangwon,Ki, Chang Do,Kim, Hasuck,Chang, Ji Young
, p. 5544 - 5549 (2007/10/03)
We demonstrated the possibility of modifying the selectivity of a two-point binding imprinted polymer by chemical modification of the binding sites inside the cavities. We used a thermally reversible bond for the preparation of the monomer-template complex, which allowed us to remove the template easily by means of a simple thermal reaction and to simultaneously introduce various functional groups into the cavity. A phenylmaleimide having an azidocarbonyl group was reacted with diethylstilbestrol (DES, template) to yield a monomer, where the template was linked to two polymerizable maleimido groups via a thermally reversible urethane bond. The polymerization of the monomer was carried out in the presence of ethylene glycol dimethacrylate (EGDMA) by the initiation with 2,2-azobis(isobutyronitrile) (AIBN) at 54°C in DMF. The polymers were refluxed in 1,4-dioxane in the presence of a nucleophile such as water, methanol, or aniline. In this extraction step, the template molecules were removed from the polymer matrix, and simultaneously the isocyanato groups, which were generated by the thermal cleavage of the urethane bond, were converted to amino, urethane, or urea groups through their reaction with water, methanol, or aniline, respectively. The specific recognition ability of the imprinted polymers for the template and its structural analogues was dependent on the space between the two binding points as well as on the nature of the functional group. This method is especially propitious for developing artificial receptors for molecules lacking strongly interactive groups.
Human insulin analogues
-
, (2008/06/13)
The present invention relates to novel human insulin analogues exhibiting a low ability to associate in solution, a method for the preparation of such insulin analogues, insulin preparations containing the human insulin analogues of the invention and a method of treating Diabetes Mellitus using these human insulin analogues.
STERICALLY-DRIVEN ANHYDRIDE FORMATION
Belletire, J. L.,Conroy, G. M.
, p. 403 - 416 (2007/10/02)
Oxidative coupling of highly substituted carboxylic acid dianions affords hindered succinic acid derivatives which undergo facile intramolecular anhydride formation.A novel, but low yield, synthetic sequence converts 4'-methoxypropiophenone into diethylstilbestrol.
Stereochemistry and Side Products in Reductive Coupling of Alkyl Aryl Ketones to 1,2-Dialkyl-1,2-diarylethylenes
Leimner, Juergen,Weyerstahl, Peter
, p. 3697 - 3705 (2007/10/02)
The reductive coupling of alkyl aryl ketones 1 - 3 and 7 - 9 by low valent titanium salts yields predominantly the (Z)-isomers of 11 - 13 and 17 - 19.Evidence is given by 1H NMR spectroscopy.This behavior can be explained by ?-complex formation of phenyl rings with Ti0.Severe steric hindrance, however, favors the (E)-isomers ( -> 14 and 15).Donor groups in p-position, particularly, give increasing amounts of pinacols, 23 - 27, which undergo rearrangement to the ketones 28 and 29.
